A chemical entity, which is potent in activity against its target, is the first step in the drug discovery process. However, a potent compound is only effective when an appropriate quantity is transported to the site of action at an acceptable rate after it has been administered. Even potent compounds benefit from optimization of these aspects. Many potent chemical entities do not have optimal pharmacokinetic parameters and hence the pharmacodynamic properties of these drugs are also suboptimal. In addition, there are several chemical entities that are already available in the market which have restricted pharmacokinetic properties and hence cannot be formulated in a manner convenient for patient administration.
The rate and extent of transportation into the blood circulation may be controlled by addition of certain groups to the original molecule, thereby modifying the molecule and its properties. Molecular modification is the chemical modification of a known and previously characterized lead compound for the purpose of enhancing its usefulness as a drug. This could mean enhancing its specificity for a particular target site, increasing its potency, improving its rate and extent of absorption, modifying the time course over which the active components become bio-available in the body (e.g., time release formulation), reducing its toxicity, and/or changing its physical or chemical properties (e.g., solubility) to optimize those aspects for particular applications.
However, the moiety used for molecular modification of the drug must be such that the therapeutic efficacy of the compound is retained and/or enhanced, while causing modification of the pharmacokinetic properties. Further, the novel compound, when administered, must not adversely affect the safety, toxicity and efficacy of the chemical entity beyond a tolerable degree.
Though there are certain methods to alter the pharmacokinetic profile of the compounds, which may or may not result in the alteration of the pharmacodynamic profiles, there are no methods available that are applicable to a wide range of drugs.
Hence there is a need for a novel method of modification of the drugs, which alter the pharmacokinetic and pharmacodynamic profile of the drugs.